Brooklyn, NY – Research led by SUNY Downstate Medical Center has identified a brain
receptor that appears to initiate adolescent synaptic pruning, a process believed
necessary for learning, but one that appears to go awry in both autism and schizophrenia.

Sheryl Smith, PhD, professor of physiology and pharmacology at SUNY Downstate, explained,
“Memories are formed at structures in the brain known as dendritic spines that communicate
with other brain cells through synapses. The number of brain connections decreases
by half after puberty, a finding shown in many brain areas and for many species, including
humans and rodents.”

This process is referred to as adolescent “synaptic pruning” and is thought to be
important for normal learning in adulthood. Synaptic pruning is believed to remove
unnecessary synaptic connections to make room for relevant new memories, but because
it is disrupted in diseases such as autism and schizophrenia, there has recently been
widespread interest in the subject.

Dr. Smith continued, “Our report is the first to identify the process which initiates
synaptic pruning at puberty. Previous studies have shown that scavenging by the immune
system cleans up the debris from these pruned connections, likely the final step in
the pruning process.

“Working with a mouse model we have shown that, at puberty, there is an increase in
inhibitory GABA receptors, which are targets for brain chemicals that quiet down nerve
cells. We now report that these GABA receptors trigger synaptic pruning at puberty
in the mouse hippocampus, a brain area involved in learning and memory.” The report,
published by eLife, “Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic
GABAA receptors on dendritic spines,” (Afroz, S., Parato, J., Shen, H. and Smith,
S.S.), is online at: http://dx.doi.org/10.7554/eLife.15106.

Dr. Smith adds that by reducing brain activity, these GABA receptors also reduce levels
of a protein in the dendritic spine, kalirin-7, which stabilizes the scaffolding in
the spine to maintain its structure. Mice that do not have these receptors maintain
the same high level of brain connections throughout adolescence.

Dr. Smith points out that the mice with too many brain connections, which do not undergo
synaptic pruning, are able to learn spatial locations, but are unable to re-learn
new locations after the initial learning, suggesting that too many brain connections
may limit learning potential.

These findings may suggest new treatments targeting GABA receptors for “normalizing”
synaptic pruning in diseases such as autism and schizophrenia, where synaptic pruning
is abnormal. Research has suggested that children with autism may have an over-abundance
of synapses in some parts of the brain. Other research suggests that prefrontal brain
areas in persons with schizophrenia have fewer neural connections than the brains
of those who do not have the condition.

The article citation is: eLife 2016;10.7554/eLife.15106.

The research leading to the results published by eLife was supported by the National Institutes of Health/National Institute of Mental Health,
Award Number R01-MH100561. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the National Institute of
Mental Health or National Institutes of Health.

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About SUNY Downstate Medical Center

SUNY Downstate Medical Center, founded in 1860, was the first medical school in the
United States to bring teaching out of the lecture hall and to the patient’s bedside.
A center of innovation and excellence in research and clinical service delivery, SUNY
Downstate Medical Center comprises a College of Medicine, College of Nursing, School
of Health Professions, a School of Graduate Studies, School of Public Health, University
Hospital of Brooklyn, and a multifaceted biotechnology initiative including the Downstate
Biotechnology Incubator and BioBAT for early-stage and more mature companies, respectively.

SUNY Downstate ranks twelfth nationally in the number of alumni who are on the faculty
of American medical schools. More physicians practicing in New York City have graduated
from SUNY Downstate than from any other medical school.